Potassium Carbonate → 5-(3-fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-one

HRID 2241258Notes

Reaction equation

HRID 2241258 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10](=[O:24])[N:11]([CH3:23])[C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[OH:8].[CH3:25][O:26][C:27]1[CH:44]=[CH:43][C:30]([CH2:31][N:32]2[C:36]3=[N:37][CH:38]=[CH:39][C:40](Cl)=[C:35]3[C:34]([CH3:42])=[N:33]2)=[CH:29][CH:28]=1.CC([O-])(C)C.[K+].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10](=[O:24])[N:11]([CH3:23])[C:12]([NH:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[N:13][CH:14]=2)[CH:5]=[CH:6][C:7]=1[O:8][C:40]1[CH:39]=[CH:38][N:37]=[C:36]2[N:32]([CH2:31][C:30]3[CH:29]=[CH:28][C:27]([O:26][CH3:25])=[CH:44][CH:43]=3)[N:33]=[C:34]([CH3:42])[C:35]=12

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 23665647Potassium tert-butoxideHCID 684185945-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-oneHCID 685123991-(4-methoxybenzyl)-4-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 685163095-(3-fluoro-4-(1-(4-methoxybenzyl)-3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-oneYield 11.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 5-(3-fluoro-4-hydroxyphenyl)-2-(4-fluorophenylamino)-3-methylpyrimidin-4(3H)-one (25.2 mg, 0.077 mmol) and 1-(4-methoxybenzyl)-4-chloro-3-methyl-1H-pyrazolo[3,4-b]pyridine (20 mg, 0.070 mmol) dissolved in DMF (0.5 mL), added KOtBu (0.077 ml, 0.077 mmol) 1M solution in THF, and potassium carbonate (10.6 mg, 0.077 mmol). The mixture was stirred at 110° C. overnight. Cooled to room temperature and partitioned between EtOAc (15 mL) and water (20 mL). The organic layer was dried with brine, Na2SO4, and evaporated to afford 27 mg of crude product. Purified by silica gel column chromatography (Biotage 12M) eluting with 5% MeOH/EtOAc to afford desired product as white solid (4.6 mg, 11%). LRMS (APCI pos) m/e 581.2 (M+1).

Workup

  1. temperatureCooled to room temperature
  2. custompartitioned between EtOAc (15 mL) and water (20 mL)
  3. dry with materialThe organic layer was dried with brine, Na2SO4
  4. customevaporated
  5. customto afford 27 mg of crude product
  6. customPurified by silica gel column chromatography (Biotage 12M)
  7. washeluting with 5% MeOH/EtOAc

Sources & evidence

ORD record
ord-d9c0dca1b8854307bc7594375bc4e82f
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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